CRCNS: Cholinergic contribution to hippocampal information processing

CRCNS：胆碱能对海马信息处理的贡献

• 批准号: 10183326
• 负责人: Carmen Castro Canavier
• 金额: $ 36.5万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10183326
• 关键词: Acetylcholine; Affect; Area; Attenuated; Behavior; Buffers; Cations; Cells; Code; Cognition Disorders; Cognitive Therapy; Complex; Computer Models; Data; Diffuse; Dose; Electrophysiology (science); Environment; Fire - disasters; Frequencies; Hippocampus (Brain); Image; Individual; Ion Channel; Lead; Learning; Location; Mediating; Memory; Mental disorders; Modeling; Myoepithelial cell; Neuromodulator; Neurons; Parvalbumins; Pattern; Pharmacology; Phase; Physiologic pulse; Play; Positioning Attribute; Process; Property; Pyramidal Cells; Ramp; Rattus; Recording of previous events; Retrieval; Role; Route; Sensory; Shapes; Slice; Stream; Structure; Synapses; Synaptic plasticity; Testing; Therapeutic; Visit; Work; attenuation; base; cholinergic; entorhinal cortex; experimental study; hippocampal pyramidal neuron; improved; in vivo; information processing; model development; neurotransmitter release; optogenetics; patch clamp; place fields; predictive modeling; prospective; relating to nervous system; response; two-photon

Area CA 1 of the hippocampus plays a key role in learning and memory. CA 1 pyramidal neurons receive two major input streams, one from the entorhinal cortex that mediates sensory information about the external world, and another from area CA3 that mediates retrieval of previously stored representations. The neuromodulator acetylcholine (ACh) is thought to gate encoding and retrieval. Our preliminary results indicate that ACh, by activating the Ca2+-activated nonspecific cation current ICAN and modulating other ion channels, dramatically affects the intrinsic response to a triangular current ramp simulating the excitatory input, thus levels of ACh may regulate the pattern of place field firing by shifting the peak to later positions in ramp. This shift could cause the coding to shift from prospective, representing upcoming locations, to retrospective, representing recently visited locations, which may favor encoding over retrieval. Our preliminary data also shows that ACh can induce sustained firing; since novelty increases ACh levels, this persistent firing may facilitate the synaptic plasticity required to form new place fields. Moreover, we find that there are both intrinsic and synaptic mechanisms that endow CA 1 pyramidal neurons with low pass filtering capabilities specific to the Schaffer collateral (SC) inputs from CA3, and that these capabilities are switched off by ACh. In Aim 1, we test the hypothesis that cholinergic modulation converts the shape of the rate response to a triangular current ramp from decelerating to accelerating in a dose-dependent fashion, with a concomitant shift in the peak. In Aim 2, we test the hypotheses that intrinsic properties of CA 1 neurons mediate low pass filtering of SC inputs, with a critical additional component provided by parvalbumin-positive (PV+) basket cells, and that cholinergic modulation removes the low pass filtering, such that CA 1 can follow higher input frequencies from CA3. This work seeks to elucidate the neural bases of complex behaviors and mental illnesses. Better understanding of the mechanisms underlying cholinergic modulation of neuronal ensembles may lead not only to an improved understanding of information processing important in learning and memory, but eventually to improved therapies for cognitive disorders.

海马ca1区在学习和记忆中起着关键作用。ca1锥体神经元接收两个

项目成果

Phase response theory explains cluster formation in sparsely but strongly connected inhibitory neural networks and effects of jitter due to sparse connectivity.

相位响应理论解释了稀疏但强连接的抑制神经网络中的簇形成以及稀疏连接引起的抖动影响。

• DOI: 10.1152/jn.00728.2018
• 发表时间: 2019
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Tikidji-Hamburyan,RubenA;Leonik,ConradA;Canavier,CarmenC
• 通讯作者: Canavier,CarmenC

Shunting Inhibition Improves Synchronization in Heterogeneous Inhibitory Interneuronal Networks with Type 1 Excitability Whereas Hyperpolarizing Inhibition Is Better for Type 2 Excitability.

分流抑制可改善具有 1 型兴奋性的异质抑制性中间神经元网络的同步性，而超极化抑制则更适合 2 型兴奋性。

• DOI: 10.1523/eneuro.0464-19.2020
• 发表时间: 2020
• 期刊: eNeuro
• 影响因子: 3.4
• 作者: Tikidji-Hamburyan,RubenA;Canavier,CarmenC
• 通讯作者: Canavier,CarmenC

Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons.

钠通道的长期失活作为 CA1 锥体神经元的适应机制。

• DOI: 10.1523/jneurosci.1914-21.2022
• 发表时间: 2022
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Upchurch,CarolM;Combe,CrescentL;Knowlton,ChristopherJ;Rousseau,ValeryG;Gasparini,Sonia;Canavier,CarmenC
• 通讯作者: Canavier,CarmenC